Is MAT1A p.Asp179Val (c.536A>T) pathogenic?

MAT1A p.Asp179Val (c.536A>T) is classified Uncertain significance in MAT1A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-08). AlphaMissense: likely pathogenic (0.9964); Absent from gnomAD v4.1; Associated with methionine adenosyltransferase deficiency.

What condition is associated with MAT1A p.Asp179Val (c.536A>T)?

MAT1A p.Asp179Val (c.536A>T) is associated with methionine adenosyltransferase deficiency (ClinVar).

How common is MAT1A p.Asp179Val (c.536A>T) in the general population?

MAT1A p.Asp179Val (c.536A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAT1A p.Asp179Val (c.536A>T)?

AlphaMissense predicts likely pathogenic (score 0.9964) — an in-silico prediction, not a clinical call.

MAT1A p.Asp179Val

Q: How is Methionine adenosyltransferase I/III deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.536A>T · rs2492495891 · VCV2003423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9964 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

methionine adenosyltransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.9964	likely pathogenic · top 3% in MAT1A
REVEL	0.918	moderately pathogenic-leaning
SaProt	LLR -13.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 16 kb · p 6.1e-09 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAT1A
Protein: p.Asp179Val
Coding: c.536A>T
MANE Select: NM_000429
dbSNP: rs2492495891
Type: single nucleotide variant
Location: chr10:80280186 (GRCh38)
Gene constraint: LOEUF 0.653 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 96.77 · 4 PDB
Residue 179: a β-strand; a binding site

Full MAT1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

methionine adenosyltransferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Methionine adenosyltransferase I/III deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

MAT1A p.Asp179Glu Uncertain significance ★ ⚠ same residue
MAT1A p.Ala259Val Pathogenic ★★ same condition
MAT1A p.Arg199Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
MAT1A p.Arg199His Pathogenic ★★ ⚠ same condition
MAT1A p.Arg264Cys Pathogenic ★★ same condition
MAT1A p.Arg264His Pathogenic ★★ same condition
MAT1A p.Arg292Cys Pathogenic/Likely pathogenic ★★ same condition
MAT1A p.Arg299Cys Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mat1a-p-asp179val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown